Immunotherapy + SBRT for Metastatic Breast Cancer

Recruiting in Palo Alto (17 mi)

+4 other locations

Overseen by Silvia Formenti, M.D.

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Weill Medical College of Cornell University

Must be taking: CDK4/6 inhibitors, Aromatase inhibitors

Must not be taking: Systemic chemotherapy, HER2-neu therapy

Disqualifiers: Connective tissue disorders, Immunodeficiency, Autoimmune disease, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

Women with Hormone Receptor (HR)+ Human Epidermal growth factor Receptor (HER)2- metastatic breast cancer are eligible to a randomized trial. Patients receiving standard first line therapy for metastatic HR+ Breast cancer(BC) (letrozole+palbociclib) are randomly assigned to also receive Stereotactic Body Radiation Therapy(SBRT) to each metastatic lesion.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those currently using systemic chemotherapy, endocrine therapy, or HER2-neu targeted therapy. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination of palbociclib and letrozole for metastatic breast cancer?

Research shows that combining palbociclib with letrozole significantly improves progression-free survival (the time during and after treatment that a patient lives with the disease without it getting worse) in patients with hormone receptor-positive, HER2-negative metastatic breast cancer compared to letrozole alone. ^{1 2 3 4 5}

Is the combination of immunotherapy and SBRT for metastatic breast cancer safe?

The combination of palbociclib and letrozole, used for advanced breast cancer, has shown an acceptable safety profile, with neutropenia (a low level of neutrophils, a type of white blood cell) being the most common side effect. There is a case report of acute lymphoblastic leukemia in a patient treated with these drugs, highlighting the importance of long-term monitoring. ^{2 6 7 8 9}

What makes the Immunotherapy + SBRT treatment for metastatic breast cancer unique?

This treatment combines immunotherapy with stereotactic body radiotherapy (SBRT), a precise form of radiation that targets cancer cells while sparing healthy tissue. It is unique because it integrates local radiation with systemic immunotherapy, potentially enhancing the body's immune response to cancer, which is not a standard approach for metastatic breast cancer. ^{10 11 12 13 14}

Research Team

Silvia Formenti, M.D.

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

This trial is for women over 18 with HR+ HER2- metastatic breast cancer, who can receive CDK4/6 inhibitors and aromatase inhibitors. They must have adequate organ function, no more than five measurable disease sites, and not be on certain therapies or have active infections or autoimmune diseases.

Inclusion Criteria

My cancer has spread to 5 or fewer places in my body.

I am premenopausal based on my last period, hormone therapy, or blood hormone levels.

You need to have at least 100,000 platelets per microliter of blood.

Exclusion Criteria

I have another cancer besides the one being studied that has progressed or needed treatment in the last 3 years.

I have brain metastases that are not under control.

I have a tumor larger than 5 cm.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Letrozole and Palbociclib, with I-SBRT for Arm 2, starting Letrozole alone and adding Palbociclib on day 21 after I-SBRT completion

Up to 36 months

Daily visits for I-SBRT, regular visits for medication administration

Radiation

Stereotactic Body Radiation Therapy (SBRT) is administered to each metastatic lesion, alternating daily to accommodate a 48-hour interval between fractions

≤ 12 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of ctDNA levels, ORR, adverse events, and overall survival

Up to 36 months

Treatment Details

Interventions

• Letrozole (Aromatase Inhibitor)
• Palbociclib (CDK4/6 Inhibitor)
• Stereotactic Body Radiation Therapy (SBRT) (Radiation)

Trial Overview The study tests if adding Stereotactic Body Radiation Therapy (SBRT) to standard first-line treatment (letrozole and palbociclib) improves outcomes in metastatic breast cancer. Participants are randomly assigned to either the combined treatment group or the standard therapy group.

Participant Groups

Group I: ARM 2 - Letrozole and Palbociclib + I-SBRT Active Control 3 Interventions

Patients randomized to arm 2 will start letrozole alone, and add palbociclib on day 21, after completion of I-SBRT. Treatment may be given daily (to keep the total I-SBRT treatment time to ≤ 12 days) and lesions targeted with I-SBRT will thus be alternated each day to accommodate for the 48 hour interval between fractions.

Group II: ARM 1 - Letrozole and Palbociclib Active Control 2 Interventions

Patients randomized to arm 1 will start standard Letrozole followed by Palbociclib at day 21.

Letrozole is already approved in Canada for the following indications:

Approved in Canada as Letrozole for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

UPMC Hillman Cancer Center Pittsburgh, PA

Brooklyn Methodist Hospital - NewYork Presbyterian New York, NY

Houston Methodist Cancer Center Houston, TX

Weill Cornell Medicine New York, NY

More Trial Locations

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1103

Patients Recruited

1,157,000+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of first-line palbociclib plus letrozole versus letrozole alone for HR+/HER2- metastatic breast cancer in US real-world clinical practice. DeMichele, A., Cristofanilli, M., Brufsky, A., et al.[2022]

Palbociclib, an inhibitor of CDK4 and CDK6, was granted accelerated FDA approval for treating advanced breast cancer in postmenopausal women when combined with letrozole, based on a trial involving 165 patients that showed significant improvement in progression-free survival (PFS).

The trial demonstrated a nearly 50% reduction in the risk of disease progression for patients receiving the combination therapy compared to those on letrozole alone, although the most common side effect noted was neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer. Beaver, JA., Amiri-Kordestani, L., Charlab, R., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up. Rugo, HS., Finn, RS., Diéras, V., et al.[2023]

Oral palbociclib is an effective treatment for HR-positive, HER2-negative advanced or metastatic breast cancer, significantly prolonging progression-free survival when used with letrozole or fulvestrant in clinical trials involving postmenopausal women.

The most common side effect was neutropenia, which was manageable and rarely led to serious complications, indicating that palbociclib can be safely administered without significantly compromising its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer. Kim, ES., Scott, LJ.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Cohort Study of Palbociclib Treatment in Postmenopausal Patients With Unresectable and Metastatic Hormone Receptor-Positive Breast Cancer: Study Protocol for a CSPOR-BC Palbociclib Cohort Trial. Narui, K., Ishikawa, T., Taira, N., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib with Letrozole in Postmenopausal Women with ER+/HER2- Advanced Breast Cancer: Hematologic Safety Analysis of the Randomized PALOMA-2 Trial. Diéras, V., Harbeck, N., Joy, AA., et al.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of palbociclib in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with preexisting conditions: A post hoc analysis of PALOMA-2. Gelmon, K., Walshe, JM., Mahtani, R., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Lymphoblastic Leukemia in a Patient Treated with Letrozole and Palbociclib. Park, JH., Park, H., Kim, KH., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of palbociclib in combination with letrozole as first-line treatment of ER-positive, HER2-negative, advanced breast cancer: expanded analyses of subgroups from the randomized pivotal trial PALOMA-1/TRIO-18. Finn, RS., Crown, JP., Ettl, J., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of extra-cranial stereotactic body radiotherapy for metastatic breast cancer: Treatment indication matters. Tan, H., Cheung, P., Louie, AV., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of stereotactic radiotherapy and targeted therapy: patterns-of-care survey in German-speaking countries. Kroeze, SGC., Fritz, C., Basler, L., et al.[2020]

Stereotactic Body Radiation Therapy (SBRT) demonstrated excellent local control rates of 98% at 1 year and 90% at 2 and 3 years in 33 patients with oligometastatic breast cancer, indicating its efficacy in managing limited metastatic disease.

The treatment was well tolerated with no severe toxicities (G3-4), suggesting that SBRT is a safe option for patients with 1-3 lung and liver lesions who are not candidates for surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy: A promising chance for oligometastatic breast cancer. Scorsetti, M., Franceschini, D., De Rose, F., et al.[2017]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Survival Associated with Local Tumor Response Following Multisite Radiotherapy and Pembrolizumab: Secondary Analysis of a Phase I Trial. Luke, JJ., Onderdonk, BE., Bhave, SR., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attitudes and beliefs toward the use of stereotactic body radiotherapy in oligometastatic breast cancer: A commentary on a survey of Canadian Medical Oncologists. Donovan, E., Dhesy-Thind, S., Mukherjee, S., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of first-line palbociclib plus letrozole versus letrozole alone for HR+/HER2- metastatic breast cancer in US real-world clinical practice. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up. [2023]

4. France pubmed.ncbi.nlm.nih.gov

Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer. [2022]

5. Canada pubmed.ncbi.nlm.nih.gov

Prospective Cohort Study of Palbociclib Treatment in Postmenopausal Patients With Unresectable and Metastatic Hormone Receptor-Positive Breast Cancer: Study Protocol for a CSPOR-BC Palbociclib Cohort Trial. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Palbociclib with Letrozole in Postmenopausal Women with ER+/HER2- Advanced Breast Cancer: Hematologic Safety Analysis of the Randomized PALOMA-2 Trial. [2020]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of palbociclib in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with preexisting conditions: A post hoc analysis of PALOMA-2. [2021]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Acute Lymphoblastic Leukemia in a Patient Treated with Letrozole and Palbociclib. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of palbociclib in combination with letrozole as first-line treatment of ER-positive, HER2-negative, advanced breast cancer: expanded analyses of subgroups from the randomized pivotal trial PALOMA-1/TRIO-18. [2022]

10. Ireland pubmed.ncbi.nlm.nih.gov

Outcomes of extra-cranial stereotactic body radiotherapy for metastatic breast cancer: Treatment indication matters. [2021]

11. Germany pubmed.ncbi.nlm.nih.gov

Combination of stereotactic radiotherapy and targeted therapy: patterns-of-care survey in German-speaking countries. [2020]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy: A promising chance for oligometastatic breast cancer. [2017]

13. United States pubmed.ncbi.nlm.nih.gov

Improved Survival Associated with Local Tumor Response Following Multisite Radiotherapy and Pembrolizumab: Secondary Analysis of a Phase I Trial. [2021]

14. United States pubmed.ncbi.nlm.nih.gov

Attitudes and beliefs toward the use of stereotactic body radiotherapy in oligometastatic breast cancer: A commentary on a survey of Canadian Medical Oncologists. [2020]